Implementing Geriatric Assessment for Dose Optimization of Cyclin-dependent Kinase (CDK) 4/6-inhibitors in Older Breast Cancer Patients

Официальное название

Implementing Geriatric Assessment for Dose Optimization of CDK 4/6-inhibitors in Older Breast Cancer Patients - a Pragmatic Randomized-controlled Trial (IMPORTANT Trial)

Обзор

IMPORTANT study is a multicenter, open-label, prospective, randomized-controlled, non-inferiority trial with a pragmatic approach involving older patients (≥ 70 years old) with advanced hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer, not amenable for curative treatment and without prior therapy for advanced disease, who are suitable to receive CDK 4/6-inhibitors plus endocrine therapy as first line therapy. The study implements two approaches with high level of evidence, namely the use of comprehensive geriatric assessment (CGA) approach in treatment decision making and the use of CDK 4/6-inhibitors as the initial treatment of choice, to investigate whether a common clinical practice (starting dose reduction of CDK 4/6-inhibitors in older patients) with evidence of low certainty can be standardized using a more individualized-based approach. On the basis of baseline CGA assessment, patients will either receive full dose of CDK 4/6-inhibitors plus endocrine therapy (if patients are fit according to CGA) or be randomized to full dose vs. reduced initial dose of CDK 4/6-inhibitors (if vulnerable or frail according to CGA). The study hypothesis is that adjusting the dose according to vulnerability will allow patients to tolerate treatment better without jeopardizing the treatment efficacy. This project has received funding from the European Union's HORIZON 2022 research and innovation actions supporting the implementation of the Mission on Cancer under grant agreement No 101104589.

Вмешательства

• Препарат CDK 4/6 inhibitors
  Either Palbociclib, Ribociclib or Abemaciclib
• Препарат Endocrine therapy
  Either Letrozole, Anastrozole, Exemestane or Fulvestrant in combination with CDK 4/6-inhibitor

Первичные конечные точки

• Time to treatment failure [Срок оценки: Up to 5 years from treatment initiation]

Вторичные конечные точки (8)

• Overall treatment utility (OTU) [Срок оценки: Three months after treatment initiation]
• Overall survival [Срок оценки: Up to 5 years from treatment initiation]
• Progression free survival [Срок оценки: Up to 5 years from treatment initiation]
• Time to chemotherapy initiation [Срок оценки: Up to 5 years from treatment initiation]
• Frequency of adverse events [Срок оценки: Up to 5 years from treatment initiation]
• Assessment of Quality of life [Срок оценки: Until disease progression, participant / physician decision to stop, death, or up to 24 months from treatment initiation whichever occurs first]
• Time until Quality of life deterioration [Срок оценки: Until disease progression, participant / physician decision to stop, death, or up to 24 months from treatment initiation whichever occurs first]
• Cost effectiveness [Срок оценки: Up to 24 months from treatment initiation]

Критерии участия

Критерии включения

The following inclusion criteria will be applied:

• Patients male or female aged at least 70 years old at the time of informed consent.
• Histologically or cytologically confirmed diagnosis of HR-positive (defined as estrogen-receptor ≥ 1%), HER2-negative breast cancer according to analysis of the most recent tumor specimen by local laboratory.
• Advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative treatment.
• No prior systemic treatment for advanced disease (recurrence during neo-/adjuvant endocrine therapy is allowed). A prior period of treatment with aromatase inhibitors or fulvestrant for up to 28 days from the CDK 4/6-inhibitor initiation is allowed.
• Adjuvant treatment with CDK 4/6-inhibitors is allowed provided a disease-free interval from treatment end >12 months.
• Either measurable disease or non-measurable bone only disease, but evaluable according to RECIST criteria 1.1.
• Written informed consent prior to any study-specific procedures.
• Adequate organ function as defined in the summary of product characteristics (SmPC) for the CDK 4/6-inhibitors that is planned to be used.
• Able to swallow capsules.
• Able to understand and consent in English language or in native language for each participating country.

Критерии исключения

Eligible patients will be excluded if they have one of the following criteria:

• Patients considered from treating physician as non-suitable for treatment with CDK 4/6-inhibitors.
• Contraindications according to SmPC for the CDK 4/6-inhibitors that is planned to be used.
• Presence of visceral crisis, lymphangitis carcinomatosis, or leptomeningeal carcinomatosis.
• History of any other cancer (except of non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years.
• Participating in other interventional trial.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Греция · 5 центров

• Fourth Oncology Department & Comprehensive Clinical Trials Center, Metropolitan Hospital — Athens
• Second Department of Medical Oncology, Hygeia Hospital — Athens
• Division of Oncology, Department of Medicine, University Hospital, University of Patras Me — Pátrai
• Medical Oncology Unit, S. Andrew Hospital — Pátrai
• Second Department of Medical Oncology, Euromedica General Clinic — Thessaloniki

Италия · 2 центра

• Radiation Oncology Unit - Oncology Department, Azienda Ospedaliero Universitaria Careggi — Florence
• "Sandro Pitigliani" Department of Medical Oncology, Hospital of Prato — Prato

Швеция · 2 центра

• Department of Oncology, Örebro University Hospital — Örebro
• Department of Oncology, Uppsala University Hospital — Uppsala

Финляндия · 1 центр

• Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and Unive — Helsinki

Норвегия · 1 центр

• Department of Oncology, Akershus University Hospital (AHUS) — Oslo

Испания · 1 центр

• Department of Medical Oncology, Hospital Clinic of Barcelona — Barcelona

Публикации

• Valachis A, Biganzoli L, Christopoulou A, Fjermeros K, Fountzila E, Geisler J, Gomez-Bravo R, Karihtala P, Kosmidis P, Koutras A, Linardou H, Lindman H, Martinez-Ballestero I, Rodriguez AB, Meattini I, Munoz-Mateu M, Othman M, Psyrri A, Risi E, Schiza A, Spathas N, Utriainen M, Visani L, Ballesteros S, Basdekis I, Hay SD, Fotis T, Fricker S, de Graaf G, Jenset M, Kanters T, Lampropoulos K, Markou PMID 39431459

Идентификаторы

NCT: NCT06044623 · 280232

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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